260-2017-02-01

Rick Gilmore
2017-02-08 08:44:27

Visualizing the microanatomy of the brain (4:29)

Today's Topics

• Cells of the nervous system
  • Glia
  • Neurons
• How do these cells communicate?

How many neurons and glia?

• Old "lore": ~100 billion neurons
• New estimate (Azevedo et al. 2009)
  • ~86 +/- 8 billion neurons
  • 85 +/- 9 billion glia
• 100-500 trillion synapses, 1 billion/mm^3

Glia (neuroglia)

• "Glia" means glue
• Functions
  • Structural support
  • Metabolic support
  • Brain development
  • Neural plasticity?

Astrocytes

• "Star-shaped"
• Physical and metabolic support
  • Blood/brain barrier
  • Ion (Ca++/K+) buffering
  • Neurotransmitter (e.g., glutamate) buffering

Astrocytes

• Shape brain development, synaptic plasticity
• Regulate local blood flow
• Regulate/influence communication between neurons, (Bazargani and Attwell 2016)
• Disruption linked to cognitive impairment, disease (Chung et al. 2015)

Astrocytes

Myelinating cells

• Produce myelin or myelin sheath
• White, fatty substance
• Surrounds many neurons
• The "white" in white matter
• Provide electrical/chemical insulation
• Make neuronal messages faster, less susceptible to noise

Types of myelin-producing cells

• Oligodendrocytes
  • In brain and spinal cord (CNS)
  • 1:many neurons
• Schwann cells
  • In PNS
  • 1:1 neuron
  • Facilitate neuro-regeneration

Oligodendrocytes

Schwann Cells

Microglia

• Phagocytosis
• Clean-up damaged, dead tissue
• Prune synapses in normal development and disease
• Disruptions in microglia pruning -> impaired functional brain connectivity and social behavior, (Zhan et al. 2014)

Microglia

Microglia in red invading dentate gyrus.

Neurons

Fun facts about neurons

• Specialized for electrical & chemical communication
• Post-mitotic -- don't divide
• Most born early in life, (Bhardwaj et al. 2006)
• Among longest-lived cells in body, may scale with organism lifespan (Magrassi, Leto, and Rossi 2013)
• Can extend over long distances

Macrostructure of neurons

• Dendrites
• Soma (cell body)
• Axons
• Terminal buttons (boutons)

Structure of neurons

Dendrites

• Branch-like "extrusions" from cell body
• Majority of input to neuron
• Cluster close to cell body/soma
• Usually receive info
• Passive (do not regenerate electrical signal) vs. active (regenerate signal)
• Spines

Dendrites

Dendritic Spines

Soma (cell body)

• Varied shapes
• Nucleus
  • Chromosomes
• Organelles
  • Mitochonrdria
  • Smooth and Rough Endoplasmic reticulum (ER)

Soma

Axons

• Another branch-like "extrusion" from soma
• Extend farther than dendrites
• Usually transmit info
• Parts
  • Initial segment (closest to soma, unmyelinated)
  • Nodes of Ranvier (unmyelinated segments along axon)
  • Terminals, axon terminals, terminal buttons, synaptic terminals, synaptic boutons

Axons

Synaptic bouton (terminal button)

• Synapse (~5-10K per neuron)
• Presynaptic membrane (sending cell) and postsynaptic (receiving cell) membrane
• Synaptic cleft -- space between cells
• Synaptic vesicles
  • Pouches of neurotransmitters
• Autoreceptors (detect NTs); transporters (transport NTs across membrane)

Synaptic bouton (terminal button)

Classifying neurons

• Functional role
  • Input (sensory), output (motor/secretory), interneurons
• Anatomy
  • Unipolar
  • Bipolar
  • Multipolar

Classifying neurons

• By specific anatomy
  • Pyramidal cells
  • Stellate cells
  • Purkinje cells
  • Granule cells

Neurons by type

Neural communication

• Electrical
  • Fast(er)
  • Within neurons
• Chemical
  • Slow(er)
  • Between neurons

How are messages generated?

• Electrical potential (== voltage)
  • Think of potential energy
  • Voltage ~ pressure
  • Energy that will be released if something changes

Potential energy

Types of neural electrical potentials

• Resting potential
• Action potential

Resting potential

• Measurement
  • Electrode on inside
  • Electrode on outside
  • Inside - Outside = potential

Resting potential

Resting potential

• Neuron (and other cells) have potential energy
  • Inside neuron is -60-70 mV, with respect to outside
  • About 1/20th typical AAA battery
• Like charges repel, opposites attract, so
  • Positively charged particles pulled in
  • Negatively charged particles pushed out

Where does the resting potential come from?

• Ions
• Ion channels
• Separation between charges
• A balance of forces

We are the champIONs, my friend

• Potassium, K+
• Sodium, Na+
• Chloride, Cl-
• Organic anions, A-

Party On

• Annie (A-) was having a party.
  • Used to date Nate (Na+), but now sees Karl (K+)
• Hired bouncers called
  • "The Channels"
  • Let Karl and friends in or out, keep Nate out
• Annie's friends (A-) and Karl's (K+) mostly inside
• Nate and friends (Na+) mostly outside
• Claudia (Cl-) tagging along

Party On

Next time

• Neural communication

Azevedo, Frederico AC, Ludmila RB Carvalho, Lea T Grinberg, José Marcelo Farfel, Renata EL Ferretti, Renata EP Leite, Roberto Lent, Suzana Herculano-Houzel, and others. 2009. “Equal Numbers of Neuronal and Nonneuronal Cells Make the Human Brain an Isometrically Scaled-up Primate Brain.” Journal of Comparative Neurology 513 (5). Wiley Online Library: 532–41.

Bazargani, Narges, and David Attwell. 2016. “Astrocyte Calcium Signaling: The Third Wave.” Nature Neuroscience 19 (2): 182–89. doi:[10.1038/nn.4201](https://doi.org/10.1038/nn.4201).

Bhardwaj, Ratan D., Maurice A. Curtis, Kirsty L. Spalding, Bruce A. Buchholz, David Fink, Thomas Björk-Eriksson, Claes Nordborg, et al. 2006. “Neocortical Neurogenesis in Humans Is Restricted to Development.” Proceedings of the National Academy of Sciences 103 (33): 12564–8. doi:[10.1073/pnas.0605177103](https://doi.org/10.1073/pnas.0605177103).

Chung, Won-Suk, Christina A. Welsh, Ben A. Barres, and Beth Stevens. 2015. “Do Glia Drive Synaptic and Cognitive Impairment in Disease?” Nature Neuroscience 18 (11): 1539–45. doi:[10.1038/nn.4142](https://doi.org/10.1038/nn.4142).

Magrassi, L., K. Leto, and F. Rossi. 2013. “Lifespan of Neurons Is Uncoupled from Organismal Lifespan.” Proceedings of the National Academy of Sciences 110 (11): 4374–9. doi:[10.1073/pnas.1217505110](https://doi.org/10.1073/pnas.1217505110).

Zhan, Yang, Rosa C. Paolicelli, Francesco Sforazzini, Laetitia Weinhard, Giulia Bolasco, Francesca Pagani, Alexei L. Vyssotski, et al. 2014. “Deficient Neuron-Microglia Signaling Results in Impaired Functional Brain Connectivity and Social Behavior.” Nature Neuroscience 17 (3): 400–406. doi:[10.1038/nn.3641](https://doi.org/10.1038/nn.3641).